TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16956	51091;51092;51093	chr2:178611263;178611262;178611261	chr2:179475990;179475989;179475988
N2AB	15315	46168;46169;46170	chr2:178611263;178611262;178611261	chr2:179475990;179475989;179475988
N2A	14388	43387;43388;43389	chr2:178611263;178611262;178611261	chr2:179475990;179475989;179475988
N2B	7891	23896;23897;23898	chr2:178611263;178611262;178611261	chr2:179475990;179475989;179475988
Novex-1	8016	24271;24272;24273	chr2:178611263;178611262;178611261	chr2:179475990;179475989;179475988
Novex-2	8083	24472;24473;24474	chr2:178611263;178611262;178611261	chr2:179475990;179475989;179475988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-111
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5447
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/A	rs1250320003	None	0.17	N	0.185	0.121	0.312001716656	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs1250320003	None	0.17	N	0.185	0.121	0.312001716656	gnomAD-4.0.0	1.30271E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.61135E-05	0	3.2078E-05
T/I	rs1040561744	0.179	0.1	D	0.251	0.281	0.427254322456	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	0	5.84E-05	None	0	5.66E-05	None	0	None	0	0	0
T/I	rs1040561744	0.179	0.1	D	0.251	0.281	0.427254322456	gnomAD-4.0.0	2.05468E-06	None	None	None	None	I	None	0	4.48773E-05	None	0	2.53627E-05	None	0	0	0	0	0
T/K	rs1040561744	-0.054	0.991	N	0.535	0.451	0.519889284407	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.67336E-04
T/K	rs1040561744	-0.054	0.991	N	0.535	0.451	0.519889284407	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	3.16456E-03	0	0	0
T/K	rs1040561744	-0.054	0.991	N	0.535	0.451	0.519889284407	gnomAD-4.0.0	3.10166E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	3.29598E-04	2.54423E-06	0	0
T/S	rs1250320003	-0.438	0.885	N	0.383	0.143	0.353548585375	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
T/S	rs1250320003	-0.438	0.885	N	0.383	0.143	0.353548585375	gnomAD-4.0.0	6.84915E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99928E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0855	likely_benign	0.0797	benign	-0.428	Destabilizing	0.17	N	0.185	neutral	N	0.508993292	None	None	I
T/C	0.4568	ambiguous	0.4594	ambiguous	-0.398	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	I
T/D	0.3703	ambiguous	0.3355	benign	0.193	Stabilizing	0.993	D	0.555	neutral	None	None	None	None	I
T/E	0.256	likely_benign	0.2344	benign	0.181	Stabilizing	0.993	D	0.537	neutral	None	None	None	None	I
T/F	0.2937	likely_benign	0.2809	benign	-0.701	Destabilizing	0.986	D	0.653	neutral	None	None	None	None	I
T/G	0.2777	likely_benign	0.2544	benign	-0.633	Destabilizing	0.953	D	0.519	neutral	None	None	None	None	I
T/H	0.2989	likely_benign	0.2728	benign	-0.777	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	I
T/I	0.1632	likely_benign	0.161	benign	0.009	Stabilizing	0.1	N	0.251	neutral	D	0.53867384	None	None	I
T/K	0.2182	likely_benign	0.2056	benign	-0.385	Destabilizing	0.991	D	0.535	neutral	N	0.504119126	None	None	I
T/L	0.1307	likely_benign	0.1249	benign	0.009	Stabilizing	0.807	D	0.465	neutral	None	None	None	None	I
T/M	0.1094	likely_benign	0.1038	benign	-0.114	Destabilizing	0.996	D	0.555	neutral	None	None	None	None	I
T/N	0.1325	likely_benign	0.1229	benign	-0.321	Destabilizing	0.998	D	0.475	neutral	None	None	None	None	I
T/P	0.6845	likely_pathogenic	0.5944	pathogenic	-0.105	Destabilizing	0.991	D	0.559	neutral	D	0.593113702	None	None	I
T/Q	0.2224	likely_benign	0.2053	benign	-0.41	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	I
T/R	0.2052	likely_benign	0.1839	benign	-0.169	Destabilizing	0.991	D	0.561	neutral	N	0.509431111	None	None	I
T/S	0.1065	likely_benign	0.1029	benign	-0.555	Destabilizing	0.885	D	0.383	neutral	N	0.506519155	None	None	I
T/V	0.1212	likely_benign	0.1243	benign	-0.105	Destabilizing	0.591	D	0.407	neutral	None	None	None	None	I
T/W	0.721	likely_pathogenic	0.673	pathogenic	-0.742	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
T/Y	0.3714	ambiguous	0.3361	benign	-0.441	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.